UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

Huang, Chu‐Yu; Chen, Yan; Dai, Huaiqian; Zhang, Huan; Xie, Minyu; Zhang, Hanbin; Chen, Feilong; Kang, Xiangjin; Bai, Xia; Chen, Zhenguo

doi:10.1038/s41418-019-0350-5

Cited by 70 publications

(135 citation statements)

References 49 publications

(65 reference statements)

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“…S2A, B). These results show that UBAP2L is a general component of stress granules, consistent with recent data (Huang et al, 2019).…”

Section: Resultssupporting

confidence: 93%

“…These results show that UBAP2L is a general component of stress granules and it is not only required for arsenite-induced stress granule assembly (Markmiller et al, 2018; Youn et al, 2018) but also for stress granules assembly in other stress conditions, consistent with recent data (Huang et al, 2019). It is interesting that UBAP2L is required for stress granule assembly in heat-shock conditions.…”

Section: Resultssupporting

confidence: 92%

“…4 F). The upstream role of UBAP2L is also consistent with recent work showing that depletion of UBAP2L results in the loss of the interaction of G3BP2 with ribosomal subunits (Huang et al, 2019).…”

Section: Discussionsupporting

confidence: 89%

“…UBAP2L is required for stress granule assembly in cells stressed with arsenite, H 2 O 2 and Sorbitol (Huang et al, 2019; Markmiller et al, 2018; Youn et al, 2018). We next tested whether UBAP2L was also required for stress granule assembly in the conditions that we tested above (ER stress, proteasome inhibition, heat shock and mitochondrial stress).…”

Section: Resultsmentioning

confidence: 99%

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Molecularly distinct cores coexist inside stress granules

Cirillo

Cieren

Gotta

2019

Preprint

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L.C.), 15 monica.gotta@unige.ch (M.G.) 16 17 18 RESULTS 76UBAP2L localizes inside stress granules in discrete particles distinct from G3BP1 77 cores. 78 Given the importance of UBAP2L in sodium arsenite (arsenite hereafter)-induced stress 79 granule assembly (Markmiller et al., 2018; Youn et al., 2018), we sought to investigate its 80 sublocalization inside stress granules. To this end, we used 3D-STED (3D Stimulated 81 Emission Depletion miscroscopy, Hell and Wichmann, 1994; Klar and Hell, 1999). 3D-STED 82 immunofluorescence of HeLa K cells fixed and stained with anti-UBAP2L antibodies, 83 revealed that each stress granule is formed by discrete UBAP2L particles of roughly round 84 shape ( Fig. 1 A), with a diameter of 187.0 ± 44.2 nm (mean ± SD, Fig. 1 B). We also 85 performed 3D-STED on HeLa K cells stained for the known stress granule component 86 G3BP1 and measured the diameter of G3BP1 cores ( Fig. 1 A). Our analysis revealed a 87 diameter of 182.7 ± 41.9 nm (mean ± SD), which is in good agreement with the published 88 diameter of 190.8 ± 28.3 nm (Fig. 1B, Jain et al., 2016). The number of UBAP2L and G3BP1 89 particles linearly correlated with the stress granule volume ( Fig. S1 A). The localization of 90 UBAP2L in discrete particles and their size distribution suggest that UBAP2L localizes to 91 stress granule cores. 92The shell and the core of stress granules do not only differ in their composition, but also in 93 the dynamics of their components, with core proteins being more stable and shell proteins 94 more dynamic. To assess whether UBAP2L particles are stress granule cores, we measured 95 the dynamics of UBAP2L in living cells. To visualize UBAP2L, we tagged endogenous 96 UBAP2L at the C-terminus with the red fluorescent protein mScarlet using CRISPR-Cas9 97 (Fig. S1 B Bindels et al., 2017). Clones were screened via PCR (Polymerase Chain 98 Reaction, Fig. S1 C) and validated with western blot using an anti-UBAP2L antibody (Fig. 99 S1 D). In addition, treatment of UBAP2L-mScarlet HeLa cells with a siRNA directed against 100 mScarlet, followed by western blot analysis, confirmed the successful insertion of the 101 construct (Fig. S1 E). Although we failed to identify a homozygous insertion (Fig. S1 D, E), 102 live cell imaging revealed that UBAP2L-mScarlet transitions from a diffuse cytosolic signal 103 to a droplet-like pattern following arsenite exposure (Fig. S1 F). This observation is 104 consistent with published immunofluorescence of UBAP2L (Markmiller et al., 2018; Youn et 105 al., 2018), indicating that UBAP2L-mScarlet recapitulates the localization of wild-type 106 UBAP2L. Having created a tool to visualize UBAP2L in vivo, we next measured the 107 dynamics of UBAP2L in stress granules using Fluorescence Recovery after Photobleaching 108 (FRAP). After treating UBAP2L-mScarlet HeLa cells with arsenite to induce stress granule 109 6 formation, we bleached a single cytosolic granule and followed the fluorescence recovery 110 over time using confocal microscopy (Fig. 1 C). Analysis of fluo...

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“…S2A, B). These results show that UBAP2L is a general component of stress granules, consistent with recent data (Huang et al, 2019).…”

Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Molecularly distinct cores coexist inside stress granules

Cirillo

Cieren

Gotta

2019

Preprint

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“…Recently, a report indicated that UBAP2L modulates stress granule (SG) assembly (21). SGs are non-membranous cytoplasmic foci composed of non-translating messenger ribonucleoproteins (22).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

Yoshida

Kajiyama

Inami³

et al. 2019

In Vivo

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Background: Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. Materials and Methods: Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. Results: Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. Conclusion: Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

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Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

Dao

Castañeda

2020

BioEssays

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Liquid-liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin-binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is connected to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells.

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UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

Cited by 70 publications

References 49 publications

Molecularly distinct cores coexist inside stress granules

Molecularly distinct cores coexist inside stress granules

Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

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